Breakthrough Discovery Links New Gene to Autism
- A recent study published in The American Journal of Human Genetics has uncovered a previously unknown genetic link to autism spectrum disorder (ASD).
- ASD is a group of neurodevelopmental disorders characterized by challenges in communication, social interactions, and behavior.
- The research, conducted by teams at The Hospital for Sick Children (SickKids) in Canada and the Istituto Giannina Gaslini in Italy, involved clinical testing of 10 individuals with...
Variants in DDX53 and other X-linked genes offer genetic insights into the higher prevalence of ASD in males.
A recent study published in The American Journal of Human Genetics has uncovered a previously unknown genetic link to autism spectrum disorder (ASD). Researchers identified that variants in the DDX53 gene, located on the X chromosome, contribute to ASD, shedding new light on the genetic factors underlying the condition.
ASD is a group of neurodevelopmental disorders characterized by challenges in communication, social interactions, and behavior. It is more prevalent in males than females. Although the DDX53 gene is known for its role in brain development and function, this study is the first to establish a definitive connection between DDX53 variants and autism.
The research, conducted by teams at The Hospital for Sick Children (SickKids) in Canada and the Istituto Giannina Gaslini in Italy, involved clinical testing of 10 individuals with ASD from 8 different families. The results revealed that variants in DDX53 were maternally inherited and present in these individuals, with the majority being male. This finding underscores the potential role of DDX53 in the male predominance observed in ASD.
“By pinpointing DDX53 as a key player, particularly in males, we can better understand the biological mechanisms at play and improve diagnostic accuracy for individuals and their families,” says senior author Dr. Stephen Scherer, Senior Scientist, Genetics & Genome Biology and Chief of Research at SickKids, and Director of the McLaughlin Centre at the University of Toronto.
“Identifying this new gene as a confirmed contributor to ASD underscores the complexity of autism and the need for comprehensive genetic analysis.”
Additional Genetic Insights
At the same location on the X chromosome, the researchers found evidence that another gene, PTCHD1-AS, might be involved in autism. The study highlights a case where a boy and his mother, both with autism with little support needs, had a specific gene deletion involving the DDX53 gene and parts of PTCHD1-AS.
The study cohort was assembled through an international collaborative effort, involving several renowned clinical and research institutions from Canada, Italy and the U.S. Further analysis of large autism research databases, including Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, identified 26 more individuals with ASD who had similar rare DDX53 variants to the study participants.
“These findings provide new insights into the biology of the X chromosome in ASD, providing additional evidence for the involvement of certain genes like DDX53 and FGF13, and suggesting they should be investigated further,” says Scherer.
Implications for Autism Research
The team notes that the absence of a gene similar to DDX53 in commonly used mouse models may require future researchers to reconsider how they study ASD. Since it lacks a functional equivalent in these models, findings in DDX53 cannot be easily replicated.
“Insights from this study could significantly influence the design and interpretation of autism research, particularly in developing new models. Identifying these variants is an important step towards developing more precise diagnostics and therapeutics for patients and families with ASD,” says Scherer.
Scherer also added, “both studies provide even more evidence that complex neurobehavioral conditions like autism can sometimes have simple biologic (genetic) underpinnings.”
References: “Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus” by Marcello Scala, Clarrisa A. Bradley, Jennifer L. Howe, Brett Trost, Nelson Bautista Salazar, Carole Shum, Marla Mendes, Miriam S. Reuter, Evdokia Anagnostou, Jeffrey R. MacDonald, Sangyoon Y. Ko, Paul W. Frankland, Jessica Charlebois, Mayada Elsabbagh, Leslie Granger, George Anadiotis, Verdiana Pullano, Alfredo Brusco, Roberto Keller, Sarah Parisotto, Helio F. Pedro, Laina Lusk, Pamela Pojomovsky McDonnell, Ingo Helbig, Sureni V. Mullegama, Emilie D. Douine, Rosario Ivetth Corona, Bianca E. Russell, Stanley F. Nelson, Claudio Graziano, Maria Schwab, Laurie Simone, Federico Zara and Stephen W. Scherer, 19 December 2024, The American Journal of Human Genetics.
DOI: 10.1016/j.ajhg.2024.11.003
“Chromosome X-wide common variant association study in autism spectrum disorder” by Marla Mendes, Desmond Zeya Chen, Worrawat Engchuan, Thiago Peixoto Leal, Bhooma Thiruvahindrapuram, Brett Trost, Jennifer L. Howe, Giovanna Pellecchia, Thomas Nalpathamkalam, Roumiana Alexandrova, Nelson Bautista Salazar, Ethan A. McKee, Natalia Rivera-Alfaro, Meng-Chuan Lai, Sara Bandres-Ciga, Delnaz Roshandel, Clarrisa A. Bradley, Evdokia Anagnostou, Lei Sun and Stephen W. Scherer, 19 December 2024, The American Journal of Human Genetics.
DOI: 10.1016/j.ajhg.2024.11.008
The study was funded by the University of Toronto McLaughlin Centre, Autism Speaks, Autism Speaks Canada, Ontario Brain Institute, the Italian Ministry for Education, University and Research and SickKids Foundation. Additional funding was provided by National Institutes of Health and the California Center for Rare Diseases at UCLA.